116313-85-0Relevant articles and documents
Improved method for demethylation of nitro-catechol methyl ethers
Learmonth, David A.,Alves, Paula C.
, p. 641 - 649 (2002)
Several nitro-catechol compounds, useful as inhibitors of COMT were obtained in excellent yield and purity via an improved procedure for demethylation of the corresponding methyl ethers using aluminium chloride and pyridine in ethyl acetate.
The inhibition of catechol O-methyltransferase and monoamine oxidase by tetralone and indanone derivatives substituted with the nitrocatechol moiety
de Beer, Andries D.,Legoabe, Lesetja J.,Petzer, Anél,Petzer, Jacobus P.
, (2021)
The enzymes, catechol O-methyltransferase (COMT) and monoamine oxidase (MAO) are important drug targets, and inhibitors of these enzymes are established therapy for symptomatic Parkinson's disease (PD). COMT inhibitors enhance the bioavailability of levodopa to the brain, and therefore are combined with levodopa for the treatment of motor fluctuations in PD. Inhibitors of the MAO-B isoform, in turn, are used as monotherapy or in conjunction with levodopa in PD, and function by reducing the central degradation of dopamine. It has been reported that 1-tetralone and 1-indanone derivatives are potent and specific inhibitors of MAO-B, while compounds containing the nitrocatechol moiety (e.g. tolcapone and entacapone) are often potent COMT inhibitors. The present study attempted to discover compounds that exhibit dual COMT and MAO-B inhibition by synthesizing series of 1-tetralone, 1-indanone and related derivatives substituted with the nitrocatechol moiety. These compounds are structurally related to series of nitrocatechol derivatives of chalcone that have recently been investigated as potential dual COMT/MAO inhibitors. The results show that 4-chromanone derivative (7) is the most promising dual inhibitor with IC50 values of 0.57 and 7.26 μM for COMT and MAO-B, respectively, followed by 1-tetralone derivative (4d) with IC50 values of 0.42 and 7.83 μM for COMT and MAO-B, respectively. Based on their potent inhibition of COMT, it may be concluded that nitrocatechol compounds investigated in this study are appropriate for peripheral COMT inhibition, which represents an important strategy in the treatment of PD.
Method for producing entacapone
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Paragraph 0050-0058, (2021/04/10)
The present invention relates to an entacapone production method, which comprises a nitration reaction, a de-methylation reaction and a condensation reaction. The nitration reaction is completed by glacial acetic acid, vanillin and 65% nitric acid within 3-5 hours; the de-methylation reaction is completed by reaction among nitrovanillin, dichloromethane, tetrabutyl ammonium bromide, anhydrous aluminum chloride and pyridine; and the condensation reaction is completed by reaction among isopropanol, 3,4-dihydroxyl-5-nitro benzaldehyde, N,N-diethyl cyanoacetamide and piperidine. The entacapone production method provided by the invention is high in yield, high in purity and stable in quality.
Pyridine Improves Aluminum Triiodide Induced Selective Cleavage of Alkyl o -Hydroxyphenyl Ethers: A Practical and Efficient Procedure for the Preparation of Hydroxychavicol by Demethylation of Eugenol
Sang, Dayong,Yao, Ming,Tian, Juan,Chen, Xiaoman,Li, Li,Zhan, Hongju,You, Linhong
, p. 138 - 142 (2016/12/26)
Demethylation of eugenol with aluminum triiodide is complicated by an unexpected hydrogenation side reaction. The hydrogenation proceeds through a cascade deprotonation, hydroiodination, and hydrogen-halogen exchange process, and can be prevented by suppressing the hydroiodination in advance. A practical demethylation procedure is thus developed that delivers hydryoxychavicol in essentially quantitative yield by using pyridine as an additive. The method is selective towards cleaving alkyl o-hydroxyphenyl ethers and is compatible with a variety of functional groups.
